Mechanisms of H2O2-induced oxidative stress in endothelial cells

Abstract

Development of an in vitro model for the early stages of cardiovascular disease is a current necessity. Cardiovascular disease is the leading cause of death in the United States and throughout the world. Oxidative stress and reactive oxygen species have been implicated in cardiovascular disease development. An in vitro model of these processes will improve our understanding of cardiovascular disease development and allow for the development of additional treatments. Atherosclerosis is an inflammatory disease and increased levels of H 2 O 2 are associated with inflammation. The model focuses on H 2 O 2-induced oxidative stress under static and shear conditions. Previous studies have documented increased O 2 .and increased cytotoxicity in smooth muscle cells exposed to H 2 O 2. Under static culture, endothelial cells exposed to H 2 O 2 , exhibited increased O 2 .over basal levels via NOS and NAPDH oxidase pathways. Increased O 2 .was attenuated by MnSOD adenoviral-mediated upregulation and endothelial cell exposure to Tiron. This suggests NOS and NADPH oxidase as sources of increased O 2 .under H 2 O 2-induced oxidative stress. Endothelial cell cytotoxicity was increased with H 2 O 2 exposure. The increase in cytotoxicity was diminished upon exposure to Tiron or L-NAME. Under shear conditions (8.2 dynes/cm 2), endothelial cells exposed to H 2 O 2 exhibited increased O 2 .compared to control via an L-NAME (specific inhibitor NOS) and Apocynin (NADPH oxidase inhibitor) inhibitable mechanism. This suggests NOS and NADPH oxidase as sources of increased O 2 .under H 2 O 2-induced oxidative stress. The increased O 2 .was attenuated with MnSOD adenoviral-mediated upregulation and endothelial cell exposure to Tiron (an O 2 .scavenger). Endothelial cell attachment under shear with exposure to H 2 O 2 was improved with MnSOD adenoviral-mediated upregulation as observed by decreased loss of the endothelial cell monolayer compared with H 2 O 2 exposed endothelial cells.

Effects of helium on inflammatory and oxidative stress-induced endothelial cell damage

“…This may indicate that the combination of helium and H 2 O 2 is strong enough to cause cell death in HUVEC. H 2 O 2 stimulation in endothelial cells leads to superoxide production via (uncoupled) nitric oxide synthase and NAPDH oxidase [31] which can induce cellular injury [32]. Treating neutrophils with hyperbaric noble gases increased formation of reactive oxygen species, mediated by collision-induced superoxide formation dependent of the properties and size of the gas used (helium oargon) [11].…”

Protective effect of sulfurous water in peripheral blood mononuclear cells of Alzheimer's disease patients

“…HP can increase the oxidative stress to cells by enhancing superoxide anion production and inactivating thiol groups of some enzymes [11,20] and it was used in both comet assay and MTT assay. On the other hand, HCY stimulates PH production in metal-mediated reactions and producing peroxynitrites [40] and it was used only in MTT assay.…”

β-elemene inhibits monocyte–endothelial cells interactions via reactive oxygen species/MAPK/NF-κB signaling pathway in vitro

“…Many of stimulators including H 2 O 2 , oxidized low-density lipoprotein (ox-LDL) and homocysteine have been indicated to promote the expression levels of CAMs in endothelial cells resulting in endothelial cells activation, dysfunction and injury (Boulden et al, 2006;Cernuda-Morollon and Ridley, 2006;Coyle et al, 2006;Wilson, 2003). Hence, the inhibition of monocyte-endothelial cells interactions may represent a therapeutic approach against atherosclerosis and other related disorders (Fuentes and Palomo, 2014).…”